Background: The opioid epidemic continues to be an ongoing public health crisis in the United States. Initially, large increases in overdose death rates were observed in largely rural, White communities, leading to the initial perception that the opioid epidemic was primarily a problem for the White population. Recent findings have shown increasing rates of overdose death among Blacks. We compare overdose rates between Blacks and Whites and explore county-level spatiotemporal heterogeneity in Ohio. Methods: We obtained county-level opioid overdose death counts for Whites and Blacks from 2007 to 2018 in Ohio. We fit a Bayesian multivariate spatial rates model to estimate annual standardized mortality ratios for Whites and Blacks for each county. We accounted for correlation between racial groups in the same county and across space and time. We also estimated differences in the mean trends between urban and rural counties for each racial group. Results: The overall overdose death rate in the state was increasing until 2018. County-level death rates for Whites were higher than Blacks throughout the state early in the study period. Death rates for Blacks increased throughout the study period and were comparable to the rates for Whites by the end of the study in many counties. Conclusions: County-level opioid overdose death rates increased faster for Blacks than Whites during the study. By 2018, death rates were comparable for Blacks and Whites in many counties. The opioid epidemic spans racial groups in Ohio and trends indicate that overdose is a growing problem among Blacks.

The 2018–2020 Ebola virus disease epidemic in Democratic Republic of the Congo (DRC) resulted in 3481 cases (probable and confirmed) and 2299 deaths. In this paper, we use a novel statistical method to analyze the individual-level incidence and hospitalization data on DRC Ebola victims. Our analysis suggests that an increase in the rate of quarantine and isolation that has shortened the infectiousness period by approximately one day during the epidemic’s third and final wave was likely responsible for the eventual containment of the outbreak. The analysis further reveals that the total effective population size or the average number of individuals at risk for the disease exposure in three epidemic waves over the period of 24 months was around 16,000–a much smaller number than previously estimated and likely an evidence of at least partial protection of the population at risk through ring vaccination and contact tracing as well as adherence to strict quarantine and isolation policies.

Human immunodeficiency virus-1 (HIV-1) is the causative agent of acquired immunodeficiency syndrome (AIDS). HIV-1, like all retroviruses, stably integrates its vDNA copy into host chromatin, a process allowing for permanent infection. This essential step for HIV-1 replication is catalyzed by viral integrase (IN) and aided by cellular protein LEDGF/ p75. In addition, IN is also crucial for proper virion maturation as it interacts with the viral RNA genome to ensure encapsulation of ribonucleoprotein complexes within the protective capsid core. These key functions make IN an attractive target for the development of inhibitors with various mechanisms of action. We conducted a high-throughput screen (HTS) of ∼370,000 compounds using a homogeneous time-resolved fluorescence-based assay capable of capturing diverse inhibitors targeting multifunctional IN. Our approach revealed chemical scaffolds containing diketo acid moieties similar to IN strand transfer inhibitors (INSTIs) as well as novel compounds distinct from all current IN inhibitors including INSTIs and allosteric integrase inhibitors (ALLINIs). Specifically, our HTS resulted in the discovery of compound 12, with a novel IN inhibitor scaffold amenable for chemical modification. Its more potent derivative 14e similarly inhibited catalytic activities of WT and mutant INs containing archetypical INSTI-and ALLINI-derived resistant substitutions. Further SAR-based optimization resulted in compound 22 with an antiviral EC 50 of ∼58 μM and a selectivity index of >8500. Thus, our studies identified a novel small-molecule scaffold for inhibiting HIV-1 IN, which provides a promising platform for future development of potent antiviral agents to complement current HIV-1 therapies.

The 2018-2020 Ebola virus disease epidemic in Democratic Republic of the Congo (DRC) resulted in 3481 cases (probable and confirmed) and 2299 deaths. In this paper, we use a novel statistical method to analyze the individual-level incidence and hospitalization data on DRC Ebola victims. Our analysis suggests that an increase in the rate of quarantine and isolation by approximately 12% during the epidemic’s third and final wave was likely responsible for the eventual containment of the outbreak. The analysis further reveals that the total effective population size or the average number of individuals at risk for the disease exposure in three epidemic waves over the period of 24 months was around 19,000—a much smaller number than previously estimated and likely an evidence of at least partial protection of the population at risk through ring vaccination and contact tracing as well as adherence to strict quarantine and isolation policies.

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